Tideglusib is a GSK-3β inhibitor. To consider the utility of tideglusib for a heterogeneous disorder such as ASD, we approach the problem by examining its potential effects on single gene syndromes that may be associated with ASD, in addition to examining pathways highlighted by the genomic approach. Pharmacological agents that can deplete GSK-3β such as Tideglusib have been shown to rescue the phenotype of the Fragile X – FMR1 knockout transgenic mouse. Rescued or improved domains included learning and memory, hyperactivity, anxiety and fear conditioning, as well as repetitive behaviors (Franklin et al., 2013) In addition, Tideglusib is brain penetrant and can be orally administered. It has been subject to investigation in Alzheimer’s Disease and Progressive Supranuclear Palsy. More than 480 patients have been exposed to tideglusib for more than a year and preliminary results suggest some favorable effects on brain volume and downstream targets (e.g. Höglinger et al., 2014, Martinez et al., 2011). It has been generally well tolerated.

Objectives: TO evaluate the efficacy of tideglusib vs. placebo for the treatment of core symptom domains in adolescents with ASD.

Methods: This is a phase II randomized, placebo controlled, multisite trial. Participants were recruited across 3 sites and were randomized to drug or placebo in 1:1 fashion. Safety was evaluated using the SMURF, safety blood work and ECG. Efficacy was evaluated using the ABC – SW as a primary measure. Secondary measures included the Vineland-II, YBOCS, RBS-R as well as measures of anxiety, sleep and parent chief complaint. pK data was collected using a sparse sampling method. Biomarkers in the AKT-ERK pathway, as well imaging markers were explored.

Results:

83 participants were randomized across 3 sites. Tideglusib was well tolerated with no related serious adverse events reported. One participant was discontinued due to elevated liver enzymes. Final efficacy data as well as pharmacokinetics, pharmacodynamics and biomarkers predicting response will be presented.

Conclusions: Tideglusib, a GsK-3β inhibitor, was well tolerated in adolescents with ASD. Efficacy and biomarker data will also be presented